Follow-up with SCSA results
5 Replies
Scott - February 14

Dr Smith:

Pasted below is our previous post to you and your response. We have since completed the SCSA test and the results are: DFI = 14.9% and HDS = 17.9%. The lab has checked the box titled "Excellent Sperm DNA Integrity." Responding to your previous question, I do not have a copy of my original sperm analysis or morphology, but was told everything is normal. We did not use ISCI in either cycle.

We have two frozen embryos remaining from our last cycle that are early stage blastocysts frozen on day 6. Based on the repeated failed transfers with what appears to be a recurring issue of "slow growing" embryos, our chances at success with these would not appear very good to me.

Do you have any thoughts on this? Any other possible explanation for these repeated failures and slower than normal embryonic growth rate? Our natural conception success rate seems so much better. Thoughts?

Thank you very much in advance for your help.

Re:good eggs but slow embryos?
« Reply #10 on: 12/15/05, 20:23 » | Reply with quote


apologize for latching on to this thread, but our situation has some similarities.
We are baffled and our RE is as well, though he has not yet had time to review everything. I'm hoping you have some thoughts or ideas. Here is the summary:

First pregnancy: conceived first month of trying, healthy boy.
Second pregnancy: conceived second month of trying, 20 week ultrsound shows borderline thickened nuchal fold, amnio shows no genetic abnormalities, stillbirth at 32 weeks (unexplained cause)
Decide on IVF due to severe hyperemesis. Use egg donor due to wife's medical history.
First IVF: Proven egg donor, proven surrogate, eight embryos progress to blastocyst. Fresh transfer 2 (failed). Thaw remaining six (do not look good following thaw). Transfer all (failed)

Start new cycle with new egg donor and new proven surrogate. Eleven embryos retrieved, all fertilized. On day 5, no expanded blastocysts. Two early blasts plus one morula transferred (failed). Only two moderately expanded blasts were viable on day six for freezing.

In both cycles, the embryos developed slowly and we did not have any expanded blastocysts on day 5 to transfer. The same donor from the second cycle did another cycle with someone else shortly after and had numerous fully expanded blasts on day 5.

The common factor is my sperm, although I have had chromosome analysis including karyotyping and everything is normal. In addition, we have not had any trouble getting pregnant naturally.

Help!! We are baffled. Is there something else about my sperm that would cause embryos to develop slowly in culture, but would not show up in chromosomal testing?

Any thoughts or ideas at all??!!

We appreciate your help.
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Dr Smith
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« Reply #11 on: 12/19/05, 09:00 » | Reply with quote


need a bit more information. Could you please post the most recent semen analysis results (including morphology) and tell me whether or nor ICSI was performed in either or both IVF cycles.

DNA fragmentation in the sperm can cause fewer embryos to reach the blastocyst stage and also cause the embryos that do reach the blastocyst stage to be of poorer quality. Even though your karyotype was normal, there may be a sperm DNA fragmentation issue. There is a test for sperm DNA fragmentation. To read up on this, see


Dr Smith - February 15

Now I'm puzzled too. It is reassuring that the SCSA results were normal. When I re-read your post I started doing some math. Embryo development doesn't look that slow and is witihin the expected range. Eight blastocysts on the first cycle, four on the next. That's not too bad. The fact that they were not fully expanded on Day 5 is not that big a deal. We have had many, many pregnancies resulting from the transfer of expanding blastocysts on Day 5. We schedule our blastocyst transfers in the early afternoon of Day 5. Embryos that are starting to expand when first observed at 8am are often fully expanded by the afternoon. The expansion process occurs very rapidly and is not the best indicator of developmental potential. The quality of the inner cell mass (# of stem cells) is far more inidcative of developmental potential that the degree of expansion. You may want to take a look at that information or ask your doctor about the condition of the inner cell mass of these embryos.

What sticks out in my mind is the crappy thaw rate. Of the 6 blastocysts that were frozen and thawed from the first cycle, it is unsual that all 6 looked crappy after thawing. Hmmm... A lab issue? Looks suspicious. I have a 90%+ survival rate for blastocyst freezing and I don't do anything special. I use a commercially available, FDA-approved kit for freezing blastocysts and a standard controlled rate freezer. In any case, it doesn't give much hope for the two frozen on Day 6 of the second cycle. I'd say go ahead and thaw them and give it a try, but don' your hopes up too much. Alternatively, you could move the embryos to another program. That [i]might[/i] improve the post-thaw survival and any embryo transfer issues (see below).

The other issue is the actual embryo transfer procedure. Some docs are better at embryo transfers than others. If the doc screws up the embryo transfer, it doesn't matter how good the embryos were. Not sure how you would investigate this as this information is usually a closely guarded secret within the program. The embryologists know who's good at transfers and who's not, but they will never tell you 'cause that would be their job.


Scott - February 15

Thank you for your reply.

If I understand you correctly, you are not necessarily concerned that the rate of our embryonic development is all that important. For whatever reason, in both cycles, embryos were reaching expanded blastocyst stage at day 6 at best. I will attempt to find out more about the quality of the inner cell mass.

Our clinic has good success rates for both frozen and fresh transfers. The 2003 data matched national averages and anecdotally, recent success rates seem significantly higher.

It is interesting that you mention transfer technique. In the first cycle with the first surrogate, he encountered a ridge that was not apparent in the mock transfer. This forced him to reload the embryos into a different catheter. Subsequent to the unsuccessful transfer, he stated that the surrogate would need a cervical dilitation prior to the next transfer. The surrogate refused this procedure and went on to other IPs and a different RE, only to be successful with twins.

I think with her success with the next couple, the crappy post-thaw embryos from the first cycle, and then the slow growing embryos and failed transfer on our second cycle, we began looking at the possibility of some sort of embryo or sperm quality issue.

Although the data must be limited since the situation is unique, have you ever heard of any subsets of people who can obtain successful conception in vivo, but have difficulty in vitro. Since we used two different egg donors, the only common factor is my sperm.

I may be reading too much into this. Perhaps the only explanation is simply the law of averages.

Thank you.


Dr Smith - February 16

You logic holds up that the only common factor was the sperm, to a point, but Im still not convinced that's the main issue. If there is a sperm problem, it usually pops up in one of three places. First, failed or severely reduced fertilization. That didn't happen. Second, severely reduced blastocyst development. When sperm genetics are a contributing problem, the vast majority of the embryos hang up either at the 4 to 8-cell stage or at the morula stage on Day 4 - they never make it to blastocyst. That didn't happen either. The third problem area is early miscarriage (i.e. in the first few weeks). The embryos that stop growing at this point (after initiating implantation) usually exhibit a reduced number of stem cells in the inner cell mass at the blastocyst stage (i.e. before transfer). At this point in time, we don't know if that was a problem for you guys or not, but since there wasn't any indication of implantation (e.g. positive hCG), it also seem unlikely. It would be helpful to know the grade of the embryos that were transferred or frozen.

From my perspective, the fertilization and embryo development seemed to be "normal" and there was no indication of a contributing sperm problem. That's why I started to look elsewhere (e.g. transfer technique). The pregnancy rate following difficult transfers (and especially ones that require a reloading of the catheter) is significantly below that of easy transfers. I think that's at least part of problem. However, that doesn't explain everything. The remainder could be just the luck of the draw.

I have seen patients that had difficultly in conceiving a second pregnancy on their own, underwent IVF and failed, and then got pregnant on their own a few months later (take that Dr HI-Tech!). So yes, it happens - but not very frequently.


Scott - February 16

First of all Dr Smith, I want to thank you for taking the time to respond in such a thoughtful and honest manner to myself and so many others that post here. It is clear that you are taking the time to fully understand the issues. I'm sure that many people that post here feel that they don't get as much attention from the physicians that they are compensating.

In any event, I guess I should provide you with a little more information on our last transfer. While I stated that it failed, I did not mention that we had positive (though very delayed HcG results:
9DP5DT = 5
10DP5DT = 11
13DP5DT = 28
15DP5DT = 78
22DP5DT = 790
27DP5DT = 2350

The ultrasound a couple of days later revealed a cellular mass that had implanted on the uterine wall but apparently no sign of a sac or any other viability. I don't remember exactly how he described it, but a D&C was not necessary.

It sounds like I need to ask our RE what the grade of the transferred blasts were as well as whether or not he knows the number of stem cells in the ICM of both the transferred and frozen blastocycsts.

Is that a number that the embryologist should know? Is it a routine part of the classification of blastocysts.

Thanks again. I hope to not bother you too much more!!


Dr Smith - February 16

Hmm... This does put a different spin on things.

What you described (I think) is what we call an "empty sac". The blastocyst stage embryo is composed of two groups of cells. The sac cells (trophectoderm) and the stem cells. The embryo implanted, and the sac cells continued to grow, but the stem cells, from which all fetal tissue is derived, failed to continue to grow. This is the third situation that I described in my previous post and could be related to a sperm problem. What we need to know now is the quality of the blastocyst stage embryos that were transferred. The embryologist will not have actually counted the stem cells (they're all stuck together in a lump - hence the term "inner cell mass"). In lieu of actual counting the stem cells, we asign a letter grade to represent the size of the inner cell mass - A's are the best, B's are O.K. and do result in pregnancies (although less frequently that A grade), C's are unlikely to result in a successful term pregnancy (and often result in an "empty sac" pregnancy such as yours) and D's are usually not transferred or frozen. In my program, we do not transfer or freeze C or D grade blastocyst embryos. I'm not sure what the policy is in your program. Try to get some information about the grade of the blastocysts. The grading will probably be in the form of a number (1-5) followed by two letters (A-D). The number represents the degree of expansion and the first letter refers to the size of the inner cell mass, the second letter refers to the appearance of the sac cells. Let me know what you find out.



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